Synthesis of cationic siloxane prepolymers

ABSTRACT

This application is directed toward an improved method of synthesizing cationic siloxane prepolymers as well as a specific cationic siloxane prepolymer having improved compatibility with monofunctional siloxanyl methacrylate monomers and medical devices containing the cationic siloxane prepolymer.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. Provisional Appln. No.60/886,675, which was filed Jan. 26, 2007.

FIELD

This application is directed toward improved methods of synthesizingcationic siloxane prepolymers as well as a specific cationic siloxaneprepolymer having improved compatibility with monofunctional siloxanylmethacrylate monomers and medical devices containing the cationicsiloxane prepolymer.

BACKGROUND OF THE INVENTION

US patent application publication number 2007/0142584 filed Jan. 27,2006, the contents of which are incorporated by reference herein,discloses certain cationic siloxane prepolymers that are able to formwater extractable medical devices as well as methods of making themonomers. An example of a monomer made according to the prior syntheticapproach is provided in Formula (I) below:

wherein n is an integer from 1 to about 300.

The method taught in US patent application publication number2007/0142584 used to synthesize a methacrylate capped cationic siloxane(bromide counter ion) is shown below:

This reaction scheme requires the use of a large excess of thepolymerization inhibitor 3,5-Di-tert-4butylhydroxytoluene (BHT) as wellas a large excess of the reactant 2-(dimethylamino)ethyl methacrylate(DMAEMA). Another inhibitor which could be used is 4-methoxyphenol(MEHQ). Even though there is a large excess of DMAEMA, this reactionoccurs at a very slow rate (100 hours at 60° C.) before productconversion nears 100%. In addition, the boiling point of DMAEMA is 182°C. Due to the cationic nature of the final product, the only way toremove the unreacted DMAEMA is with a combination of high vacuum andheat (stripping). Washing the material results in the emulsification andfractionation of the product. Also, since the product has methacrylatefunctionality, the stripping of the DMAEMA is problematic and oftenresults in premature polymerization of the reaction product. This isespecially the case as the reaction is scaled up. Therefore an improvedmethod of synthesizing cationic siloxane prepolymers would be desirable

In addition, although monomers such as those claimed in US patentapplication publication number 2007/0142584 provide medical devices thatare entirely suitable in some circumstances, it was determined thatmedical devices prepared from a monomer mix containing a higher amountof monofunctional siloxane methacrylate would be highly desirable. Wehave discovered that an iodo salt of a cationic siloxane prepolymerhaving the structural formula (II) shown below:

allows a greater amount of monofunctional siloxanyl methacrylate to beincorporated in the monomer mix than the bromo salt of a cationicsiloxane prepolymer as shown in Formula (III)

wherein n equals 39.

SUMMARY OF THE INVENTION

Provided herein are methods of making a cationic siloxane prepolymerwherein the reaction product is more easily isolated than cationicsiloxane prepolymers prepared according to a previous method. The methodcomprises, in one embodiment, reacting bis-bromobutylpolydimethylsiloxane with 2-(methylamino)ethanol in polar solvent suchas dioxane to provide a first reaction product. The first reactionproduct is then reacted with methacryloyl chloride or methacrylicanhydride in the presence of triethylamine in polar solvent such aschloroform to provide a second reaction product. The second reactionproduct is then reacted with iodomethane in tetrahydrofuran to providethe third reaction product as a cationic functionalized siloxaneprepolymer.

Also provided is an improved cationic siloxane prepolymer that providesa lens material having improved properties as compared to other cationicsiloxane polymers. The improved cationic siloxane prepolymer is amonomer having the following formula (IV):

wherein n is from 0 to 200.

BRIEF DESCRIPTION OF THE DRAWINGS

None

DETAILED DESCRIPTION

Provided herein is an improved method of making functionalized cationicsiloxane prepolymers. In one embodiment, the method comprises reacting abis-halide polysiloxane such as bis-bromobutyl polydimethylsiloxane withan alkyl functionalized hydroxy secondary amine such2-(methylamino)ethanol to provide a first reaction product. Other alkylfunctionalized hydroxy secondary amines would include 2-(ethylamino)ethanol, 2-(propylamino) ethanol, 2-(butylamino) ethanol.

The reaction is conducted in a polar solvent. Polar solvents areselected because they are able to dissolve the reactants and increasethe reaction rate. Examples of polar solvents would include ethylacetate, dioxane, THF, DMF, chloroform, etc.

The first reaction product is then reacted with a methacrylating agentto provide a second reaction product having vinyl polymerizableendgroups on the polysiloxane. Examples of methacrylating agents wouldinclude methacryloyl chloride, methacrylic anhydride, 2-isocyanatoethylmethacrylate, itaconic acid and itaconic anhydride.

Because HCl is produced during this stage of the reaction, which mayresult in deterioration of the polysiloxane, an acid scavenger such astriethylamine, triethanolamine, or 4-dimethylaminopyridine is used toreduce the amount of HCl formed during the synthesis. As utilized hereinthe expression “acid scavenger” refers to a material that reacts withany acid that is otherwise formed during the synthesis to prevent thedegradation of the reaction product.

To quaternize the amine groups in the polysiloxane of the secondreaction product an alkyl halide such as iodomethane is used as aquaternizing agent to provide the final third reaction product. Thefinal product is isolated by removal of the solvent and any residualalkyl halide from the reaction mixture.

A schematic representation of the method is provided in the reactionschematic below:

This new synthetic route divides the synthesis into three steps anddiffers dramatically from the previous procedure in that the quatfunctionality is formed at the last step of the reaction. This change insynthetic route allows for easy removal of unreacted starting materialsand significantly reduces the occurrence of premature polymerization.Use of lower levels of polymerization inhibitor in the synthesis of thecationic siloxane prepolymer is also able to be achieved.

Following the given synthetic scheme, a known amount of bis-bromobutylpolydimethylsiloxane with known molecular weight was refluxed in dioxanewith 2-(methylamino)ethanol for 72 hours at 75° C. to afford reactionproduct (1) after isolation. The structure of (1) was verified by NMRanalysis. Product (1). with chloroform as a solvent, was then allowed toreact with methacryloyl chloride in the presence of triethylamine atambient temperature to afford reaction product (2) after isolation. Thestructure of product (2) was also verified by NMR analysis. The finalstep of the synthesis was the quaternization of (2) with iodomethane,using THF as a solvent, to afford reaction product (3) after 15 hours at45° C. The structure of the final product (3) was verified by NMR, SEC,and Mass Spectrometry analyses.

The method is particularly useful for synthesizing the followingprepolymer which has desirable properties for forming a medical device.

wherein n is from 0 to 200.

A preferred monomer is shown below wherein n equals 39.

It was surprisingly discovered that use of the iodo salt of the cationicpolysiloxane prepolymer, as compared to the bromo salt form, resulted ina monomer mix having improved compatibility with the other prepolymers.Improved compatibility was demonstrated by a visual comparison madebetween the two formulations. Greater than 3% of a monofunctionalpolysiloxane material caused cloudiness in the formulation made with thebromo salt of a cationic siloxane prepolymer, while up to 4.5%monofunctionial polysiloxane material was added to a formulation madewith the iodo salt of a cationic siloxane prepolymer without cloudinessresulting. This improved compatibility results in a monomer mix thatallows increased concentrations of mono functional comonomers resultingin a polymerized product having improved physical properties.

In a further aspect, the invention includes articles formed of deviceforming monomer mixes comprising the prepolymers of formula (IV).According to preferred embodiments, the article is the polymerizationproduct of a mixture comprising the aforementioned cationic siloxaneprepolymer of formula (II) and at least a second monomer. Preferredarticles are optically clear and useful as a contact lens.

Useful articles made with these materials may require hydrophobic,possibly silicon containing monomers. Preferred compositions have bothhydrophilic and hydrophobic monomers. The invention is applicable to awide variety of polymeric materials, either rigid or soft. Especiallypreferred polymeric materials are lenses including contact lenses,phakic and aphakic intraocular lenses and corneal implants although allpolymeric materials including biomaterials are contemplated as beingwithin the scope of this invention. Especially preferred are siliconcontaining hydrogels.

The present invention also provides medical devices such as heart valvesand films, surgical devices, vessel substitutes, intrauterine devices,membranes, diaphragms, surgical implants, blood vessels, artificialureters, artificial breast tissue and membranes intended to come intocontact with body fluid outside of the body, e.g., membranes for kidneydialysis and heart/lung machines and the like, catheters, mouth guards,denture liners, ophthalmic devices, and especially contact lenses.

Silicon containing hydrogels are prepared by polymerizing a mixturecontaining at least one silicon-containing monomer and at least onehydrophilic monomer. The silicon-containing monomer may function as acrosslinking agent (a crosslinker being defined as a monomer havingmultiple polymerizable functionalities) or a separate crosslinker may beemployed.

An early example of a silicon-containing contact lens material isdisclosed in U.S. Pat. No. 4,153,641 (Deichert et al assigned to Bausch& Lomb Incorporated). Lenses are made from poly(organosiloxane) monomerswhich are α, ω terminally bonded through a divalent hydrocarbon group toa polymerized activated unsaturated group. Various hydrophobicsilicon-containing prepolymers such as1,3-bis(methacryloxyalkyl)-polysiloxanes were copolymerized with knownhydrophilic monomers such as 2-hydroxyethyl methacrylate (HEMA).

U.S. Pat. No. 5,358,995 (Lai et al) describes a silicon containinghydrogel which is comprised of an acrylic ester-capped polysiloxaneprepolymer, polymerized with a bulky polysiloxanylalkyl (meth)acrylatemonomer, and at least one hydrophilic monomer. Lai et al is assigned toBausch & Lomb Incorporated and the entire disclosure is incorporatedherein by reference. The acrylic ester-capped polysiloxane prepolymer,commonly known as M₂ D_(x) consists of two acrylic ester end groups and“x” number of repeating dimethylsiloxane units. The preferred bulkypolysiloxanylalkyl (meth)acrylate monomers are TRIS-type(methacryloxypropyl tris(trimethylsiloxy)silane) with the hydrophilicmonomers being either acrylic- or vinyl-containing.

Other examples of silicon-containing monomer mixtures which may be usedwith this invention include the following: vinyl carbonate and vinylcarbamate monomer mixtures as disclosed in U.S. Pat. Nos. 5,070,215 and5,610,252 (Bambury et al); fluorosilicon monomer mixtures as disclosedin U.S. Pat. Nos. 5,321,108; 5,387,662 and 5,539,016 (Kunzler et al);fumarate monomer mixtures as disclosed in U.S. Pat. Nos. 5,374,662;5,420,324 and 5,496,871 (Lai et al) and urethane monomer mixtures asdisclosed in U.S. Pat. Nos. 5,451,651; 5.648,515; 5,639,908 and5,594,085(Lai et al), all of which are commonly assigned to assigneeherein Bausch & Lomb Incorporated, and the entire disclosures of whichare incorporated herein by reference.

Examples of non-silicon hydrophobic materials include alkyl acrylatesand methacrylates.

The cationic siloxane prepolymer may be copolymerized with a widevariety of hydrophilic monomers to produce silicon hydrogel lenses.Suitable hydrophilic monomers include: unsaturated carboxylic acids,such as methacrylic and acrylic acids; acrylic substituted alcohols,such as 2-hydroxyethylmethacrylate and 2-hydroxyethylacrylate: vinyllactams, such as N-vinyl pyrrolidone (NVP) and 1-vinylazonam-2-one; andacrylamides, such as methacrylamide and N,N-dimethylacrylamide (DMA).

Still further examples are the hydrophilic vinyl carbonate or vinylcarbamate monomers disclosed in U.S. Pat. No. 5,070,215, and thehydrophilic oxazolone monomers disclosed in U.S. Pat. No. 4,910,277.Other suitable hydrophilic monomers will be apparent to one skilled inthe art.

Hydrophobic cross-linkers would include methacrylates such as ethyleneglycol dimethacrylate (EGDMA) and allyl methacrylate (AMA). In contrastto traditional silicon hydrogel monomer mixtures, the monomer mixturescontaining the quaternized siloxane prepolymer of the invention hereinare relatively water soluble. This feature provides advantages overtraditional silicon hydrogel monomer mixtures in that there is less riskof incompatibility phase separation resulting in hazy lenses and thepolymerized materials are extractable with water. However, when desired,traditional organic extraction methods may also be used. In addition,the extracted lenses demonstrate a good combination of oxygenpermeability (Dk) and low modulus, properties known to be important toobtaining desirable contact lenses. Moreover, lenses prepared with thequaternized siloxane prepolymers of the invention herein are wettableeven without surface treatment, provide dry mold release, do not requiresolvents in the monomer mix (although solvents such as glycerol may beused) the extracted polymerized material is not cytotoxic and thesurface is lubricious to the touch. In cases where the polymerizedmonomer mix containing the quaternized siloxane prepolymers of theinvention herein do not demonstrate a desirable tear strength,toughening agents such as TBE (4-t-butyl-2-hydroxycyclohexylmethacrylate) may be added to the monomer mix. Other strengtheningagents are well known to those of ordinary skill in the art and may alsobe used when needed.

Although an advantage of the cationic siloxane prepolymers disclosedherein is that they are relatively water soluble and also soluble intheir comonomers, an organic diluent may be included in the initialmonomeric mixture. As used herein, the term “organic diluent”encompasses organic compounds which minimize incompatibility of thecomponents in the initial monomeric mixture and are substantiallynonreactive with the components in the initial mixture. Additionally,the organic diluent serves to minimize phase separation of polymerizedproducts produced by polymerization of the monomeric mixture. Also, theorganic diluent will generally be relatively non-inflammable.

Contemplated organic diluents include tert-butanol (TBA); diols, such asethylene glycol and propylene glycol; and polyols, such as glycerol.Preferably, the organic diluent is sufficiently soluble in theextraction solvent to facilitate its removal from a cured article duringthe extraction step.

Other suitable organic diluents would be apparent to a person ofordinary skill in the art.

The organic diluent is included in an amount effective to provide thedesired effect. Generally, the diluent is included at 5 to 60% by weightof the monomeric mixture, with 10 to 50% by weight being especiallypreferred.

According to the present process, the monomeric mixture, comprising atleast one hydrophilic monomer, at least one cationic siloxane prepolymerand optionally the organic diluent, is shaped and cured by conventionalmethods such as static casting or spincasting.

Lens formation can be by free radical polymerization such asazobisisobutyronitrile (AIBN) and peroxide catalysts using initiatorsand under conditions such as those set forth in U.S. Pat. No. 3,808,179,incorporated herein by reference. Photo initiation of polymerization ofthe monomer mixture as is well known in the art may also be used in theprocess of forming an article as disclosed herein. Colorants and thelike may be added prior to monomer polymerization.

Subsequently, a sufficient amount of unreacted monomer and, whenpresent, organic diluent is removed from the cured article to improvethe biocompatibility of the article. Release of non-polymerized monomersinto the eye upon installation of a lens can cause irritation and otherproblems. Unlike other monomer mixtures that must be extracted withflammable solvents such as isopropyl alcohol, because of the propertiesof the novel quaternized siloxane prepolymers disclosed herein,non-flammable solvents including water may be used for the extractionprocess.

Once the biomaterials formed from the polymerized monomer mix containingthe cationic siloxane prepolymers monomers disclosed herein are formedthey are then extracted to prepare them for packaging and eventual use.Extraction is accomplished by exposing the polymerized materials tovarious solvents such as water, tert-butanol, etc. for varying periodsof time. For example, one extraction process is to immerse thepolymerized materials in water for about three minutes, remove the waterand then immerse the polymerized materials in another aliquot of waterfor about three minutes, remove that aliquot of water and then autoclavethe polymerized material in water or buffer solution.

Following extraction of unreacted monomers and any organic diluent, theshaped article, for example an RGP lens, is optionally machined byvarious processes known in the art. The machining step includes lathecutting a lens surface, lathe cutting a lens edge, buffing a lens edgeor polishing a lens edge or surface. The present process is particularlyadvantageous for processes wherein a lens surface is lathe cut, sincemachining of a lens surface is especially difficult when the surface istacky or rubbery.

Generally, such machining processes are performed before the article isreleased from a mold part. After the machining operation, the lens canbe released from the mold part and hydrated. Alternately, the articlecan be machined after removal from the mold part and then hydrated.

EXAMPLES

All solvents and reagents were obtained from Sigma-Aldrich, Milwaukee,Wis., and used as received with the exception of aminopropyl terminatedpoly(dimethylsiloxane), 900-1000 and 3000 g/mol, obtained from Gelest,Inc., Morrisville, Pa., andmethacryloxypropyltris(trimethylsiloxy)silane, obtained from SilarLaboratories, Scotia, N.Y., which were both used without furtherpurification. The monomers 2-(hydroxyethyl) methacrylate and1-vinyl-2-pyrrolidone were purified using standard techniques.

Analytical Measurements

NMR: ¹H-Nuclear Magnetic Resonance (NMR) characterization is carried outusing a 400 MHz Varian spectrometer using standard techniques in theart. Samples are dissolved in chloroform-d (99.8 atom % D), unlessotherwise noted. Chemical shifts are determined by assigning theresidual chloroform peak at 7.25 ppm. Peak areas and proton ratios aredetermined by integration of baseline separated peaks. Splittingpatterns (s=singlet, d=doublet, t=triplet, q=quartet, m=multiplet,br=broad) and coupling constants (J/Hz) are reported when present andclearly distinguishable.

SEC: Size Exclusion Chromatography (SEC) analyses are carried out byinjection of 100 μL of sample dissolved in tetrahydrofuran (THF) (5-20mg/mL) onto a Polymer Labs PL Gel Mixed Bed E (×2) column at 35° C.using a Waters 515 HPLC pump and HPLC grade THF mobile phase flow rateof 1.0 mL/min, and detected by a Waters 410 Differential Refractometerat 35° C. Values of M_(n), M_(w), and polydispersity (PD) is determinedby comparison to Polymer Lab Polystyrene narrow standards.

ESI-TOF MS. The electrospray (ESI) time of flight (TOF) MS analysis wasperformed on an Applied Biosystems Mariner instrument. The instrumentoperated in positive ion mode. The instrument is mass calibrated with astandard solution containing lysine, angiotensinogen, bradykinin(fragment 1-5) and des-Pro bradykinin. This mixture provides aseven-point calibration from 147 to 921 m/z. The applied voltageparameters are optimized from signal obtained from the same standardsolution.

Stock solutions of the polymer samples are prepared as 1 mg/mL intetrahydrofuran (THF). From these stock solutions, samples are preparedfor ESI-TOF MS analysis as 30 μM solutions in isopropanol (IPA) with theaddition of 2% bv volume saturated NaCl in IPA, Samples are directlyinfused into the ESI-TOF MS instrument at a rate of 35 μL/min.

Mechanical properties and Oxygen Permeability: Modulus and elongationtests arc conducted according to ASTM D-1708a, employing an Instron(Model 4502) instrument where the hydrogel film sample is immersed inborate buffered saline; an appropriate size of the film sample is gaugelength 22 mm and width 4.75 mm, where the sample further has endsforming a clog bone shape to accommodate gripping of the sample withclamps of the Instron instrument, and a thickness of 200+50 microns.

Oxygen permeability (also referred to as Dk) is determined by thefollowing procedure. Other methods and/or instruments may be used aslong as the oxygen permeability values obtained therefrom are equivalentto the described method. The oxygen permeability of silicone hydrogelsis measured by the polarographic method (ANSI Z80.20-1998) using an O2Permeometer Model 201T instrument (Createch, Albany, Calif. USA) havinga probe containing a central, circular gold cathode at its end and asilver anode insulated from the cathode. Measurements are taken only onpre-inspected pinhole-free, flat silicone hydrogel film samples of threedifferent center thicknesses ranging from 150 to 600 microns. Centerthickness measurements of the film samples may be measured using aRehder ET-1 electronic thickness gauge. Generally, the film samples havethe shape of a circular disk. Measurements are taken with the filmsample and probe immersed in a bath containing circulating phosphatebuffered saline (PBS) equilibrated at 35° C.±0.2°. Prior to immersingthe probe and film sample in the PBS bath, the film sample is placed andcentered on the cathode premoistened with the equilibrated PBS, ensuringno air bubbles or excess PBS exists between the cathode and the filmsample, and the film sample is then secured to the probe with a mountingcap, with the cathode portion of the probe contacting only the filmsample. For silicone hydrogel films, it is frequently useful to employ aTeflon polymer membrane, e.g., having a circular disk shape, between theprobe cathode and the film sample. In such cases, the Teflon membrane isfirst placed on the pre-moistened cathode, and then the film sample isplaced on the Teflon membrane, ensuring no air bubbles or excess PBSexists beneath the Teflon membrane or film sample. Once measurements arecollected, only data with correlation coefficient value (R2) of 0.97 orhigher should be entered into the calculation of Dk value. At least twoDk measurements per thickness, and meeting R2 value, are obtained. Usingknown regression analyses, oxygen permeability (Dk) is calculated fromthe film samples having at least three different thicknesses. Any filmsamples hydrated with solutions other than PBS are first soaked inpurified water and allowed to equilibrate for at least 24 hours, andthen soaked in PHB and allowed to equilibrate for at least 12 hours. Theinstruments are regularly cleaned and regularly calibrated using RGPstandards. Upper and lower limits are established by calculating a ±8.8%of the Repository values established by William J. Benjamin, et al., TheOxygen Permeability of Reference Materials, Optom Vis Sci 7 (12s): 95(1997), the disclosure of which is incorporated herein in its entirety:

Material Name Repository Values Lower Limit Upper Limit Fluoroperm 3026.2 24 29 Menicon EX 62.4 56 66 Quantum II 92.9 85 101

Abbreviations

-   MI-MR-C12

-   NVP 1-Vinyl-2-pyrrolidone-   TRIS Methacryloxypropyltris(trimethylsiloxy)silane-   HEMA 2-Hydroxyethyl methacrylate-   v-64 2,2′-Azobis(2-methylpropionitrile)-   PG 1,3-Propanediol-   EGDMA Ethylene glycol dimethacrylate-   SA 2-[3-(2H-Benzotriazol-2-yl)-4-hydroxyphenyl]ethyl methacrylate-   IMVT 1,4-bis[4-(2-methacryloxyethyl)phenylamino]anthraquinone

Liquid monomer solutions containing cationic end-cappedpoly(dimethylsiloxane) prepolymers from examples below, along with otheradditives common to ophthalmic materials (diluent, initiator, etc.) areclamped between silanized glass plates at various thicknesses andpolymerized using thermal decomposition of the free-radical generatingadditive by heating 2 h at 100° C. under a nitrogen atmosphere. Each ofthe formulations affords a transparent, tack-free, insoluble film.

Films are removed from glass plates and hydrated/extracted in deionizedH₂O for a minimum of 4 hours, transferred to fresh deionized H2O andautoclaved 30 min at 121° C. The cooled films are then analyzed forselected properties of interest in ophthalmic materials. Mechanicaltests are conducted in borate buffered saline according to ASTM D-1708a,discussed above. The oxygen permeabilities, reported in Dk (or barrer)units, are measured in phosphate buffered saline at 35° C., usingacceptable films with three different thicknesses, as discussed above.

Unless otherwise specifically stated or made clear by its usage, allnumbers used in the examples should be considered to be modified by theterm “about” and to be weight percent.

Example 1 Synthesis of 1,3-bis(4-bromobutyl)tetramethyldisiloxaneRD-1862 “Iodo M2D39 Plus”

This example details the synthetic procedure for the production of theintermediate, 1,3-bis(4-bromobutyl)tetramethyldisiloxane.

I. Preparation of 1,3-bis(4-bromobutyl)tetramethyldisiloxane

Materials

-   -   1,3-bis(4-hydroxybutyl)tetramethyldisiloxane, vacuum stripped at        60° C. and 0.6 mbar for 2 hours    -   Aliquot® 336 (reg. trademark of Henkel Corporation), as received        Toluene (99.5%), as received    -   Hydrobromic acid (48%) aqueous HBr), as received    -   Saturated NaCl    -   0.5 M Sodium Bicarbonate solution    -   Magnesium Sulfate (anhydrous), as received    -   Silica gel 60 (E. Merck 7734-4), as received    -   Heptane (99%), as received    -   Methylene chloride (99.5%), as received

Equipment

-   -   5 L 3-neck round bottom Morton flask    -   Teflon bladed mechanical stirrer    -   Condenser    -   Thermometer    -   6 L separatory funnel    -   Vacuum filtration apparatus    -   House (low) vacuum setup    -   Vacuum pump, roughing    -   Chromatography column (3.5 in.×30. in.)    -   Rotary evaporator

Tolerances

-   -   Temperatures: ±2° C.    -   Times:=1 hour    -   Volumes:±10 mL    -   Weights: ±0.2 g

Preparation

-   -   1. A 5 L 3-neck round bottom Morton flask is equipped with a        Teflon bladed mechanical stirring system and a condenser.    -   2. 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane (837.2 g, 3.0        mol) is added to the flask along with 48.6 g (0.12 mol) Aliquat®        336 in toluene (1000 mL) and 2.0 L of 48% HBr (aq).    -   3. The reaction mixture is heated to 100° C. for 16 hours with        vigorous stirring.    -   4. After cooling, the organic layer is separated in a 6 L        separatory funnel.    -   5. Wash with 1×2 L, saturated NaCl, 0.5 M Sodium Bicarbonate        solution (3×500 mL).    -   6. Dry over magnesium sulfate and filter product by vacuum.    -   7. Heat product to 60° C. and remove solvents with roughing pump        (1.3 mbar). Crude yield is expected to be about 1250 g.    -   8. A silica gel column (2 kg silica gel, column 3.5 inches in        diameter and 30 inches long) is prepared by slurry packing with        heptane.    -   9. The yellow silicone liquid is placed on the silica gel        chromatography column with heptane (200 g).    -   10. Elute with 1.5 L 100% heptaiie, 1 L 100% heptane. 1 L 80%        heptane 20% methylene chloride, then 1 L 60% heptane 40%        methylene chloride until done.    -   11. Start collecting after the first 1 L collected as Fraction        “0”. The organic fractions 1 (65.6 g), 2, 3 (343 g), 4, 5.6 (33        g), 7 (31 g), 8 (19.4 g), were recombined and solvents removed        by flash vaporization by a Rotary evaporator at reduced pressure        to afford 1093.4 g of        1,3-bis(4-bromobutyl)tetramethyldisiloxaiie as a colorless        liquid.

Example 2 Synthesis of Poly(dimethylsiloxane) Terminated with CationicPolymerizable Functionality (RD-1862 “Iodo M2D39 Plus”)

This example details the synthetic procedure for the production of thefinal product, cationic methacrylate terminated poly(dimethylsiloxane),“Iodo M2D39 Plus”.

Materials

-   -   Drierite (8 mesh), as received    -   1,3-bis(4-bromobutyl)tetramethyldisiloxane (96.5%). as received    -   Octamethylcyclotetrasiloxane (D₄) (98%), as received    -   Trifluoromethanesulfonic acid (98%), as received    -   Sodium bicarbonate (99.7%), as received    -   Celite 503, as received    -   Acetone (99%), as received    -   Dry ice, as received    -   1,4-Dioxane (anhydrous, 99.8%), as received    -   2-(Methylamino)ethanol (98%), as received    -   Chloroform (anhydrous, 99%), as received    -   Brine solution    -   Deionized water    -   Magnesium sulfate (anhydrous), as received    -   Triethylamine (99.5%), as received    -   2,6-Di-tert-butyl-methylphenol (BHT) (99%), as received    -   Methacryloyl chloride (≧97%), as received    -   Sodium carbonate (99%), as received    -   Amberlyst A26 hydroxide form resin, as received    -   Tetrahydrofuran (anhydrous, 99.9%). as received    -   Iodomethane (99%), as received

Equipment

-   -   Flasks: 1000 mL round bottom (×3), 3-neck 1000 ml, round bottom,        500 mL    -   pressure flask (round bottom)    -   Teflon bladed mechanical stirrer    -   Drying tube    -   Pressure filter (stainless steel)    -   Nitrogen gas    -   PTFE filter (5 μm)    -   Magnetic stir plate    -   Magnetic stir bar    -   Thermometers    -   Vacuum pump, roughing    -   Vacuum traps    -   1 L Heating mantle    -   Temperature controller with thermocouple    -   Condenser (water-cooled)    -   Rubber septa    -   Rotary evaporator    -   Separatory funnel (1000 mL)    -   Vacuum filtration apparatus    -   Glass microfiber filter paper (retains samples down to 0.7 μm)    -   House (low) vacuum setup    -   Heat gun    -   Addition funnel (100 mL)    -   Oil bath    -   Aluminum foil    -   Refrigerator/freezer    -   Dry box (<5% relative humidity)    -   House air (dry, oil free)    -   Funnels    -   Spatulas

Tolerances

-   -   Temperatures: ±2° C.    -   Times: ±1 hour, unless noted otherwise    -   Volumes: ±1 mL    -   Weights: ±1 g

Preparation Step 1: Ring-Opening Polymerization

-   -   1. In a 1000 mL round bottom flask equipped with an overhead        mechanical stirrer and drying tube (with Drierite),        1,3-bis(4-bromobutyl)tetramethyldisiloxane (61.3 g) and        octamethylcyclotetrasiloxane (438.7 g) are added.    -   2. Trifluoromethanesulfonic acid (1.25 g, 0.25 w/w %) is added        and stirred 24 hours at room temperature.    -   3. To the reaction is added sodium bicarbonate (7 g) and the        mixture is allowed to stir at a moderate rate for an additional        24 hours at room temperature.    -   4. The mixture is then filtered with slight positive nitrogen        pressure through a pressure filter system equipped with 5 μm        PTFE filter and a Celite pad into a 1000 mL round bottom flask.    -   5. The mixture is stirred magnetically and stripped for at least        4 hours at 80° C. and <1.3 mbar using a vacuum pump and        acetone/dry ice trap, or until collection of residual        octamethylcyclotetrasiloxane is essentially complete (no further        collection of liquid) to afford the product as a transparent,        colorless, viscous liquid (426 g, 85% yield).        Product: 1,3-bis(4-bromobutyl) poly(dimethylsiloxane) as a        transparent colorless liquid M_(n)=1500-3000, and PD=1.5-2.5 by        gel permeation chromatography (GPC)        Step 2: Reaction with 2-(methylamino)ethanol    -   1. The colorless liquid product from step 1.5 above (200 g) was        then dissolved in 1,4-dioxane (500 mL, 2.5 mL/g dioxane to        silicone) in a 3-neck 1000 mL round bottom flask. The flask was        equipped a mechanical stirring system, a 1 L heating mantle, a        water-cooled condenser, and a thermocouple to monitor the        reaction temperature.    -   2. 2-(methylamino)ethanol (30 mL, 6 mol eq.) was added to the        reaction vessel.    -   3. The flask was sealed with rubber septum and placed under a        nitrogen purge.    -   4. The reaction was then heated for 72 hours at 100° C. and        stirred vigorously.    -   5. The contents of 3-neck 1000 mL flask were transferred to        1-neck 1000 mL round bottom flask and dioxane was removed via a        rotary evaporator.    -   6. Silicone product was redissolved in chloroform and        transferred to 1000 mL separatory funnel.    -   7. Product washed with 500 mL brine solution (2×) 500 mL 5%        sodium bicarbonate solution (3×) followed by another wash with        500 mL brine solution.    -   8. Silicone product collected from Step 2.7 and dried with        magnesium sulfate (enough to absorb all the water in the        product).    -   9. Product vacuum filtered and solvent removed with a rotary        evaporator/vacuum pump to afford intermediate product.    -   10. Product confirmed with NMR spectroscopy.        Step 3: Methacrylation with Methacryloyl Chloride    -   1. Silicone product from Step 2.9 was redissolved in anhydrous        chloroform (3.0 mL/g silicone) and transferred to 1000 mL round        bottom flask (dried with heat gun) with magnetic stir bar.    -   2. Triethylamine (6 mol eq.) was added to the reaction along        with 250 ppm BHT inhibitor.    -   3. An addition funnel (dried with heat gun) was added to the        flask and methacryloyl chloride (4 mol eq.) was added to the        funnel along with chloroform to dilute the acid chloride        (approx. twice the volume of the acid chloride). The system was        then capped with rubber septum and purged with N₂.    -   4. The reaction was stirred and the acid chloride was added        dropwise. The reaction was allowed to stir 15 hours at ambient        temperature.    -   5. Reaction transferred to 1000 mL separatory funnel and washed        with 500 mL brine solution (×2), 500 mL 5% sodium carbonate        solution (×2), and again with 500 mL brine solution.    -   6. An excess of Amberlyst A26 resin was rinsed with chloroform        and then stirred into the product from Step 3.5 for one hour.        Magnesium sulfate added to dry system.    -   7. Solids vacuum filtrated out of product and product        concentrated via rotary evaporator.    -   8. Product confirmed via NMR spectroscopy.

Step #4: Quaternization

-   -   1. Product from Step 3.7 dissolved in THF (2.0 mL/g silicone)        and transferred to 500 mL round bottom pressure flask with stir        bar.    -   2. Iodomethane (8 mol eq.) added to reaction.    -   3. Reaction vessel sealed and allowed to stir in a 45° C. oil        bath for 15 hours protected from light (wrapped in Al foil).    -   4. System placed on a rotary evaporator to remove all solvent        and excess iodomethane to afford a yellow, waxy solid product.    -   5. Product sealed and allowed to harden at approx. −20° C.    -   6. Product chopped with spatula and residual iodomethane/solvent        removed with vacuum pump (product kept at ambient temperature).    -   7. Product moved to dry box with dry air environment for        transferring, sampling, etc. and stored at −20° C. with a drying        agent to prevent moisture contamination.    -   8. Product confirmed by NMR spectroscopy, Mass Spectrometry, Gel        Permeation Chromatography, and Gas Chromatography.        Cationic methacrylate terminated poly(dimethylsiloxane)        (RD-1862. “Iodo M2D39 Plus”) as a slightly yellow, waxy-solid        product.

Example 3 Synthesis of RD-1862 “Iodo M₂D₂₉ Plus” Purpose

This document details the synthetic procedure for the production of theintermediate, 1,3-bis(4-bromobutyl)tetramethyldisiloxane and the finalproduct, cationic methacrylate terminated poly(dimethylsiloxane), “IodoM₂D₃₉ Plus”.

I. Preparation of 1,3-bis(4-bromobutyl)tetramethyldisiloxane

Materials

-   -   1,3-bis(4-hydroxybutyl)tetramethyldisiloxane, vacuum stripped at        60° C. and 0.6 mbar for 2 hours    -   Aliquot® 336 (reg. trademark of Henkel Corporation), as received        from Aldrich    -   Toluene (99.5%), as received from Aldrich    -   Hydrobromic acid (48%) aqueous HBr), as received fromn Aldrich    -   Saturated sodium chloride solution    -   0.5 M Sodium bicarbonate solution    -   Magnesium sulfate (anhydrous), as received from Fisher        Scientific    -   Silica gel 60 (E. Merck 7734-4), as received    -   Heptane (99%). as received fiom Aldrich    -   Methylene chloride (99.5%). as received from Aldrich

Equipment

-   -   5 L 3-neck round bottom Morton flask    -   Teflon bladed mechanical stirrer    -   Teflon stirrer bearing    -   Teflon sleeves    -   Condenser    -   Thermometer or thermocouple    -   6 L separatory funnel    -   Vacuum filtration apparatus    -   House (low) vacuum setup    -   Vacuum pump, roughing    -   Chromatography column (3.5 in.×30. in.)    -   Rotary evaporator

Tolerances

-   -   Temperatures: ±2° C.    -   Times: ±1 hour    -   Volumes: ±10 mL    -   Weights: ±0.2 g

Preparation

-   -   1. A 5 L 3-neck round bottom Morton flask is equipped with a        Teflon bladed mechanical stirring system and a condenser.    -   2. 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane (837.2 g. 3.0        mol) is added to the flask along with 48.6 g (0.12 mol) Aliquat®        336 in toluene (1000 mL) and 2.0 L of 48% HBr (aq).    -   3. The reaction mixture is heated to 100° C. for 16 hours with        vigorous stirring.    -   4. After cooling, the organic layer is separated in a 6 L        separatory funnel.    -   5. Wash with 1× 2 L saturated NaCl, 0.5 M Sodium Bicarbonate        solution (3×500 mL).    -   6. Dry over magnesium sulfate and filter product by vacuum.    -   7. Heat product to 60° C. and remove solvents with roughing pump        (1.3 mbar). Crude yield is expected to be about 1250 g.    -   8. A silica gel column (2 kg silica gel, column 3.5 inches in        diameter and 30 inches long) is prepared by slurry packing with        heptane.    -   9. The yellow silicone liquid is placed on the silica gel        chromatography column with heptane (200 g).    -   10. Flute with 1.5 L 100% heptane, 1 L 100% heptane, 1 L, 80%        heptane 20% methylene chloride, then 1 L 60% heptanie 40%        metlhylenie chloride until done.    -   11. Start collecting after the first 1 L collected as Fraction        “0”. The organic fractions 1 (65.6 g), 2, 3 (343 g), 4, 5, 6 (33        g), 7 (31 g), 8 (19.4 g), were recombined and solvents removed        by flash vaporization by a Rotary evaporator at reduced pressure        to afford 1093.4 g of 1,3-bis(4-bromobutyl)tetramethyldisiloxane        as a colorless liquid.

II. Synthesis of Poly(dimethylsiloxane) Terminated with CationicPolymerizable Functionality Overview:

Materials

-   -   Drierite (8 mesh), as received from Fisher Scientific    -   1,3-bis(4-bromobutyl)tetramethyldisiloxane (96.5%), made        according to above procedure    -   Octamethylcyclotetrasiloxane (D₄) (98%), as received    -   Trifluoromethanesulfonic acid (98%), as received from Aldrich    -   Sodium bicarbonate (99.7%), as received Fisher Scientific    -   Celite 503, as received from Fisher Scientific    -   Acetone (99%), as received from Aldrich    -   Dry ice    -   1,4-Dioxane (anhydrous, 99.8%), as received from Aldrich    -   2-(Methylamino)ethanol (98%), as received from Aldrich    -   Chloroform (anhydrous, 99%) as received from Aldrich    -   Saturated sodium chloride solution (Brine)    -   Deionized water    -   Magnesium sulfate (anhydrous), as received from Fisher        Scientific    -   Triethylamine (99.5%), as received from Aldrich    -   2,6-Di-tert-butyl-methylphenol (BHT) (99%), as received from        Aldrich    -   Methacrylic anhydride (≧94%), as received from Aldrich    -   Dimethylamino pyridine (97%), as received from Aldrich    -   Sodium carbonate (99%), as received from Fisher Scientific    -   Amberlyst A26 hydroxide form resin, as received from Aldrich    -   Tetrahydrofuran (anhydrous, 99.9%), as received flom Aldrich    -   Iodomethane (99%), as received from Aldrich

Equipment

-   -   Flasks: 1000 mL round bottom (1-neck), 1000 mL round bottom        (2-neck), 2000 mL round bottom (1-neck), 2000 ml round bottom        (3-neck).    -   Teflon bladed mechanical stirrer    -   Teflon stir bearing    -   Teflon sleeves    -   Teflon stoppers    -   Drying tube    -   Pressure filter (stainless steel)    -   Nitrogen gas    -   PTFE filter (5 μm)    -   Magnetic stir plate    -   Magnetic stir bars    -   Thermometers    -   Vacuum pump, roughing    -   Vacuum traps    -   2 L Heating mantle    -   Temperature controller with thermocouple    -   Condenser (water-cooled)    -   Rubber septa    -   Rotary evaporator    -   Separatory funnel (4000 mL)    -   Vacuum filtration apparatus    -   Glass microfiber filter paper (retains samples down to 0.7 μm)    -   House (low) vacuum setup    -   Heat gun    -   Addition funnel (250 mL)    -   Water bath    -   Refrigerator/freezer    -   Dry box (≦5% relative humidity)    -   House air (dry, oil free)    -   Funnels    -   Spatulas

Tolerances

-   -   Temperatures: ±2° C.    -   Times: ±1 hour, unless noted otherwise    -   Volumes: ±1 mL    -   Weights: ±1 g

Preparation Step 1: Ring-Opening Polymerization

-   -   1. In a 2-neck 1000 mL round bottom flask equipped with an        overhead mechanical stirrer and drying tube (with Drierite),        1,3-bis(4-bromobutyl)tetramethlyldisiloxane (61.3 g) and        octamethylcyclotetrasiloxane (438.7 g) are added.    -   2. Trifluoromethanesulfonic acid (1.25 g, 0.25 w/w %) is added        and stirred 24 hours at room temperature.    -   3. To the reaction is added sodium bicarbonate (7 g) and the        mixture is allowed to stir at a moderate rate for an additional        24 hours at room temperature.    -   4. The mixture is then filtered with slight positive nitrogen        pressure through a pressure filter system equipped with 5 μm        PTFE filter and a celite pad into a 1000 mL, round bottom flask.    -   5. The mixture is stirred with a magnetic stir bar and stripped        for at least 4 hours at 80° C. and <1.3 mbar using a vacuum pump        and acetone/dry ice trap, or until collection of residual        octamethylcyclotetrasiloxane is essentially complete (no further        collection of liquid) to afford the product as a transparent,        colorless, viscous liquid (426 g. 85% yield).

Step 2: Reaction with 2-(methylamino)ethanol

-   -   1. The colorless liquid product from step 1.5 above (504 g) was        then dissolved in 1,4-dioxane (504 mL, 1 mL dioxane per gram        silicone) in a 3-neck 2000 mL round bottom flask. The flask was        equipped a mechanical stirring system, a 1 L heating mantle, a        water-cooled condenser, and a thermocouple to monitor the        reaction temperature. Teflon adapters were used in all of the        flask joints to avoid silicone lubricant.    -   2. 2-(methylamino)ethanol (76 mL. 6 mol eq.) was added to the        reaction vessel.    -   3. The reaction was placed under a nitrogen blanket.    -   4. The reaction was then heated for 8 hours at 100° C. and        stirred sufficiently.    -   5. The contents of the flask were transferred to a 1-neck 2000        mL round bottom flask and dioxane was removed via a rotary        evaporator.    -   6. Silicone product was re-dissolved in chloroform (500 mL) and        transferred to 4000 mL separatory funnel (unreacted amine can be        drained from separatory funnel before washing).    -   7. Product washed with 2000 mL 50/50 brine/10% sodium        bicarbonate solution (2×), followed by a wash with 2000 mL 50/50        brine/water.,    -   8. Silicone product collected from Step 2.7 and dried with        sufficient amount of magnesium sulfate.    -   9. Product was vacuum filtered and solvent removed with a rotary        evaporator/vacuum pump.    -   10. The concentrated product was then filtered with slight        positive nitrogen pressure through a pressure filter system        equipped with 5 μm PTFE filter into a 1000 mL round bottom flask        to afford colorless intermediate product (477.6 g, 95% yield).    -   11. Product confirmed with NMR spectroscopy.

Step 3: Methacrylation with Methacrylic Anhydride

-   -   1. Silicone product from Step 2.9 (450.8 g) was re-dissolved in        anhydrous chloroform (450 mL, 1 mL/g silicone) and transferred        to a minimum of a 2-neck 2000 mL round bottom flask (dried with        heat gun) equipped with a overhead mechanical stirrer.    -   2. Triethylamine (58.9 g, 3 mol eq.) was added to the reaction,        along with dimethylamino pyridine (0.017 g, 0.001 mol eq.) and        500 ppm BHT inhibitor relative to Step 2.9 product (112.7 mg).    -   3. An addition funnel (dried with heat gun) was added to the        flask and methacrylic anhydride (67 mL. 3 mol eq.) was added to        the funnel along with chloroform to dilute the anhydride        (approx. 100 mL). The system was sealed and placed under a        nitrogen blanket.    -   4. The reaction was stirred and methacrylic anhydride was added        drop-wise. After all the anhydride was added, the reaction was        allowed to stir 15 hours at ambient temperature.    -   5. Water (approx. 700 mL) was added to the reaction and allowed        to stir until all the anhydride had converted to methacrylic        acid (approx. 15 hours).    -   6. Reaction transferred to 4000 mL separatory funnel, 700 mL        brine added to help separation, and organic layer was isolated.    -   7. Isolated product layer was washed with 2000 mL 50/50        brine/10% NaHCO3 (×2), followed by 2000 mL 50/50 brine/water.    -   8. Product transferred to 1-neck 2000 mL RBF and stirred        mechanically w/200 g Amberlyst A26 hydroxide resin (after resin        was washed w/chloroform) for 48 hours until methacrylic salt        absent from product (monitored by NMR). Note: Amberlite IRA-410        CL resin can be substituted for Amberlyst A26 hydroxide resin    -   9. Resin separated from product by vacuum filtration.    -   10. Product dried w/sufficient amount of magnesium sulfate.    -   11. Product vacuum filtered and concentrated by rotary        evaporator.    -   12. The concentrated product was then filtered with slight        positive nitrogen pressure through a pressure filter system        equipped with 5 μm PTFE filter into a 1000 mL round bottom flask        to afford intermediate product with slight yellow tint (401 g,        89% yield).    -   13. Product confirmed via NMR spectroscopy and BHT concentration        monitored by Gas Chromatography. The target level for BHT        inhibitor is 500 ppm. Appropriate amount of BHT was back-added        to methacrylated intermediate product to bring total BHT        concentration to 500±100 ppm.

Step #4: Quaternization

-   -   1. Product from Step 3.10 (250.8 g) dissolved in THF (250 mL,        1.0 mL/g silicone) and transferred to 1-neck 1000 mL round        bottom flask with magnetic stir bar.    -   2. Iodomethane (2.2 mol eq.) added to reaction.    -   3. Reaction vessel sealed with Teflon stopper and stirred in a        45° C. water bath for 7 hours.    -   4. System placed on a rotary evaporator to remove solvent and        excess iodomethane to afford a yellow, waxy solid product.    -   5. Product was sealed and allowed to harden at approx. −20° C.        for at least 2 hours.    -   6. Product moved to dry box with dry air environment (≦5%        relative humidity) to be chopped/scraped with spatula until very        fine in consistency.    -   7. Residual iodomethane/solvent removed with vacuum pump        (1.0×10⁻² mbar, product kept at ambient temperature).    -   8. Product moved back to dry box for transferring, sampling,        etc. and stored at −20° C. with a drying agent to prevent        moisture contamination (255.01 g yield).    -   9. Product confirmed by NMR spectroscopy, Mass Spectrometry and        Gel Permeation Chromatography, BHT concentration monitored by        Gas Chromatography and residual Iodomethane concentration        monitored by Liquid Chromatography.

Example 4 Preparation of film using monomer of Example 2

Parts by weight RD-1862 (Iodo salt form) 9.30 NVP 41.85 TRIS 23.25 HEMA18.6 Propylene Glycol 5.00 SA 1.50 v-64 0.50 IMVT 95 ppm

40 uL aliquots of a soluble, liquid monomer mix containing 9.3 parts byweight of the product from example 2, 23.3 parts TRIS, 41.9 parts NVP,18.6 parts HEMA, 5 parts PG, 0.5 parts v-64. 1.5 parts SA, and 95 ppmIMVT were sealed between poly(propylene) anterior and posterior contactlens moulds under an inert nitrogen atmosphere, transferred to an ovenand heated under an inert nitrogen atmosphere 2 h at 100° C. The cooledmold pairs were separated and the dry lens released from the mold,hydrated/extracted twice in deionized H2O for a minimum of 3 min.transferred to and sealed in an autoclave vial containing a bufferedsaline solution and autoclaved 30 min at 121° C. affording opticallytransparent blue-tinted ophthalmic lenses.

Example 5 Preparation of film using monomer of Example 3

RD# Parts M₂D₃₉plus 1862 5.30 M1-MCR-C12 1876 3.00 NVP 58 43.35 TRIS 14220.25 HEMA 134 18.6 UV blocker 969 1.50 vaso-64 N/A 0.50 Reactive blue322 95 ppm

Example 6 Preparation of film using monomer of Formula (III)

Parts M₂D₃₉plus (Bromo salt form) 9.30 NVP 41.85 TRIS 23.25 HEMA 18.6Propylene Glycol 5.00 SA 1.50 v-64 0.50 IMVT 95 ppm

40 uL aliquots of a soluble, liquid monomer mix containing 9.3 parts byweight of monomer of formula III, 23.3 parts TRIS, 41.9 parts NVP, 18.6parts HEMA, 5 parts PG. 0.5 parts v-64, 1.5 parts SA, and 95 ppm IMVTwere sealed between poly(propylene) anterior and posterior contact lensmoulds under an inert nitrogen atmosphere, transferred to an oven andheated under an inert nitrogen atmosphere 2 h at 100° C. The cooled moldpairs were separated and the dry lens released from the mold,hydrated/extracted twice in deionized H2O for a minimum of 3 min.transferred to and sealed in an autoclave vial containing a bufferedsaline solution and autoclaved 30 mim at 121° C. affording opticallytransparent, blue-tinted ophthalmic

Example 7 Properties of Films of Examples 4 and 6

Modulus Tensile Elong Tear Sample (GM/SQMM) (GM/SQMM) (%) (GM/MM)Example 3 111 (4) 35 (7)  38 (9)  3 (0) Example 4 116 (8) 62 (12) 76(15) 4 (0)Standard deviation is given within the parenthesis.

Example 8 Preparation of Film using Monomer of Example 2

Parts RD-1862 (Iodo salt form) 6.30 M1D11 3.00 NVP 41.85 TRIS 23.25 HEMA18.6 Propylene Glycol 5.00 SA 1.50 v-64 0.50 IMVT 95 ppm

40 uL aliquots of a soluble, liquid monomer mix containing 6.3 parts byweight of the product from example 2, 3.00 parts of a monomethacrylatedpolydimethyl siloxane prepolymer, 23.3 parts TRIS, 41.9 parts NVP, 18.6parts HEMA, 5 parts PG, 0.5 parts v-64, 1.5 parts SA, and 95 ppm IMVTwere sealed between poly(propylene) anterior and posterior contact lensmoulds under an inert nitrogen atmosphere, transferred to an oven andheated under an inert nitrogen atmosphere 2 h at 100° C. The cooled moldpairs were separated and the dry lens released from the mold,hydrated/extracted twice in deionized H2O for a minimum of 3 min,transferred to and sealed in an autoclave vial containing a bufferedsaline solution and autoclaved 30 min at 121° C. affording opticallytransparent, blue-tinted ophthalmic lenses.

Example 9 Properties of Films of Example 7

Modulus Tear Sample (GM/SQMM) (GM/MM) Example 8 77 (6) 3 (0)Standard deviation is given within the parenthesis.

1. A method of making a cationic siloxane prepolymer, the method comprising: reacting a bis-halide polysiloxane with an alkyl functionalized hydroxy secondary amine in a first polar solvent to provide a first reaction product; reacting the first reaction product with a methacrylating agent in the presence of a acid scavenger in a second polar solvent to provide a second reaction product; and reacting the second reaction product with a quaternizing agent in a third polar solvent to provide the cationic siloxane prepolymer.
 2. The method of claim 1 wherein the bis-halide polysiloxane is selected from the group consisting of bis-bromobutyl polydimethylsiloxane, bis-bromopropyl polydimethylsiloxane, bis-chloropropyl polydimethylsiloxane, and bis-3 -chlorobutyl polydimethylsiloxane.
 3. The method of claim 1 wherein the alkyl functionalized hydroxy secondary amine is selected from the group consisting of 2-(methylamino)ethanol, 2-(ethylamino) ethanol, 2-(propylamino) ethanol and 2-(butylamino) ethanol.
 4. The method of claim 1 wherein the methacrylating agent is selected from the group consisting of methacryloyl chloride, methacrylic anhydride, 2-isocyanatoethyl methacrylate, itaconic acid and itaconic anhydride.
 5. The method of claim 1 wherein the quaternizing agent is selected from the group consisting of iodomethane, iodoethane, 1 -bromobutane, and methyl chloride.
 6. The method of claim 1 further comprising the step of isolating the cationic siloxane prepolymer.
 7. A monomer having the following formula:


8. A monomer mix useful for making polymerized biomaterials comprising at least one monomer of claim 7 and at least one second monomer.
 9. The monomer mix of claim 8, further comprising in addition to the second monomer a hydrophobic monomer and a hydrophilic monomer.
 10. The monomer mix of claim 8 wherein the second monomer is selected from the group consisting of unsaturated carboxylic acids, acrylic substituted alcohols, vinyl lactams, acrylamides, methacrylates, hydrophilic vinyl carbonates, hydrophilic vinyl carbamate monomers, hydrophilic oxazolone monomers, and mixtures thereof.
 11. A device comprising a polymerization product of the monomer mixture of claim
 8. 12. The device of claim 11 wherein the device is a contact lens.
 13. The device of claim 12 wherein the contact lens is a rigid gas permeable contact lens.
 14. The device of claim 12 wherein the contact lens is a soft contact lens.
 15. The device of claim 12 wherein the contact lens is a hydrogel contact lens.
 16. The device of claim 11 wherein the device is an intraocular lens.
 17. The device of claim 16 wherein the intraocular lens is a phakic intraocular lens.
 18. The device of claim 16 wherein the intraocular lens is an aphakic intraocular lens.
 19. The device of claim 11 wherein the device is a corneal implant.
 20. The device of claim 11 wherein the device is selected from the group consisting of heart valves, intraocular lenses, films, surgical devices, vessel substitutes, intrauterine devices, membranes, diaphragms, surgical implants, blood vessels, artificial ureters, artificial breast tissue, membranes for kidney dialysis machines, membranes for heart/lung machines, catheters, mouth guards, denture liners, ophthalmic devices, and contact lenses.
 21. A method of making a device comprising: providing a monomer mixture comprising the monomer of claim 7 and at least a second monomer; subjecting the monomer mixture to polymerizing conditions to provide a polymerized device; and extracting the polymerized device.
 22. The method of claim 21 wherein the step of extracting is performed with non-flammable solvents.
 23. The method of claim 21 wherein the step of extracting is performed with water.
 24. The method of claim 21 further comprising the step of packaging and sterilizing the polymerized device.
 25. The monomer mix of claim 8 wherein the second monomer is selected from the group consisting of methacrylic acid, acrylic acid, 2-hydroxyethylmethacrylate, 2-hydroxyethylacrylate, N-vinyl pyrrolidone, N-vinyl caprolactone, methacrylamide, N-N-dimethylacrylamide, ethylene glycol dimethacrylate, methyl methacrylate, allyl methacrylate, methacryloxypropyl tris(trimethylsiloxy)silane and mixtures thereof. 